There is an increasing evidence that NK cells may play an important role in resistance against growth of tumors in vivo. However, most of the studies on NK cell-mediated cytotoxicity have been focused on in vitro studies and only limited number of investigations concerning NK cells in vivo antitumor potential have been done. The aim of this proposal is (1) to study the involvement of NK cells in in vivo resistance to the following murine tumors: acute myelogenous leukemia, B and T cell lymphoma and fibrosarcoma with metastatic properties. NK cell-deficient (homozygous being mice), NK cell-depleted (by specific anti-NK antisera) and NK cell-stimulated (by interferon-inducing pyrimidine molecules) mice will be used in these studies: (2) to study the kinetics of NK cell activities during the development and progression of the tumors and during its metastatic activities; various organs of tumor-bearing mice will be tested against a panel of tumor target cells; (3) to evaluate the therapeutic potential of interferon-inducing pyrimidine molecules, ABPP, ABmFPP and AIPP on the above mentioned tumor models, and to study the mechanism of their action; (4) to study the effect of interferon and interferon-inducingpyrimidine molecules on NK cell cytotoxic potential to tumors in vivo; (5) to study the mechanism of action of interferon-inducing pyrimidine molecules on NK cell cytotoxicity to tumors and normal tissues in vitro; (6) to study the effect of interferon and interferon-inducing pyrimidines on tumor cells blocking phenomenon. NK cell cytotoxicity will be measured in 4 hrs 51chromium release cytotoxicity assay. The following parameters will be used to determine the involvement of NK cells in tumor resistance in vivo: (a) time of tumor development, size of tumor, its metastasizing properties, clearance of tumor cells. Since NK cells appear to be important in resistance and immunosurveillance to malignancies, interferon and interferon-inducing agents considered as an anticancer therapy, and pyrimidine molecules ABPP, and ABmFPP strong interferon-inducers with virtually no toxicity, relevance of these studies of clinical situation is obvious.